Pulmonary hypertension
Safety and Efficacy of Transition From Subcutaneous Treprostinil to Oral Sildenafil in Patients With Pulmonary Arterial Hypertension

https://doi.org/10.1016/j.healun.2007.07.040Get rights and content

Background

Sildenafil is a selective inhibitor of phosphodiesterase type 5 (PDE5), and has been shown to improve 6-minute walk distance (SMWD) and World Health Organization (WHO) functional class in patients with idiopathic pulmonary arterial hypertension (iPAH) and PAH associated with connective tissue disease or with repaired congenital systemic-to-pulmonary shunts. Despite the efficacy of sildenafil in patients on conventional therapy with diuretics and anti-coagulants, little is known of the safety and efficacy of transitioning patients already established on parenteral prostanoid therapy to sildenafil.

Methods

We studied 14 patients on long-term subcutaneous treprostinil for PAH (from a cohort of 51 patients [27%]), who wished to discontinue treatment because of injection-site pain. The etiology of their PAH included iPAH (7 of 14), PAH secondary to scleroderma (2 of 14), thromboembolic disease (3 of 14) and PAH post-surgical correction of ventricular septal defect (2 of 14). Treprostinil was gradually weaned and all patients were started open-label with 50 mg sildenafil four times per day for 3 months. New York Heart Association (NYHA) functional class, SMWD, echocardiogram and quality-of-life (QOL) measures were determined at baseline and after 3 months of therapy with sildenafil.

Results

Of 14 patients, 4 discontinued the transition because of deterioration during treprostinil withdrawal, despite the introduction of sildenafil. Replacement of chronic subcutaneous treprostinil with sildenafil was possible in 10 of 14 patients (71%), who demonstrated stable NYHA class (mean ± SD: 3.1 ± 0.3 at baseline to 2.6 ± 0.8 at 3 months, p = 0.138), stable SMWD (434 ± 83 m at baseline, 451 ± 72 at 3 months, p = 0.23) and significantly improved QOL measures at 3 months.

Conclusions

The transition from subcutaneous treprostinil to sildenafil was safely achieved in most (71%), but not all, patients with pulmonary arterial hypertension of varied etiology. These patients had an improvement in both NYHA functional class and QOL, and maintained stable walk distances over a 3-month period on sildenafil therapy.

Section snippets

Inclusion Criteria

This study included patients with PAH, on long-term open-label treprostinil, who wished to withdraw from therapy because of severe injection-site pain. Patients with moderate-to-severe PAH of varied etiology, including primary PAH, PAH secondary to scleroderma or lupus (after exclusion of interstitial lung disease by high-resolution computerized tomography [CT] scan and respiratory function tests), PAH in those with history of pulmonary emboli (but <10% of the vascular tree involved on CT

Safety of Treprostinil Weaning

The 14 patients had received treprostinil for a mean of 20.2 ± 7.2 months (range 12 to 32 months). Before enrollment, treprostinil patients were weaned by 2.5 ng/kg/min/week to 50% of their usual maintenance dose, from a mean of 19.0 ± 6.8 ng/kg/min (range 7.3 to 29 ng/kg/min) to 10.4 ± 4.7 ng/kg/min (range 5 to 22 ng/kg/min) before the start of sildenafil, without worsening of symptoms.

Of the 14 patients, 1 discontinued the study after 6 weeks of sildenafil therapy. A 55-year-old man with

Discussion

This open-label study explored the potential for safe replacement of subcutaneous treprostinil therapy with oral sildenafil in patients with PAH of varied etiology. It has been demonstrated in a large double-blind, placebo-controlled study that sildenafil improves exercise capacity, WHO functional class and hemodynamics in patients with symptomatic pulmonary arterial hypertension (either idiopathic or associated with connective tissue disease or with repaired congenital systemic-to-pulmonary

References (15)

There are more references available in the full text version of this article.

Cited by (18)

  • Transition from parenteral to oral treprostinil in pulmonary arterial hypertension

    2017, Journal of Heart and Lung Transplantation
    Citation Excerpt :

    Both studies predated the approval of PDE-I therapies. The third prospective report studied patients on very low-dose subcutaneous treprostinil; 4 (of 14) participants who transitioned to sildenafil 50 mg 4 times daily failed within 3 months.11 There have been multiple retrospective studies reporting transition of patients from parenteral to inhaled prostacyclins,12,13 but no prospective reports have been published.

  • Combination therapy in pulmonary arterial hypertension

    2013, Clinics in Chest Medicine
    Citation Excerpt :

    Several small studies have shown that a minority of carefully selected, stable patients on intravenous epoprostenol or subcutaneous treprostinil can successfully be transitioned to bosentan monotherapy after a period of dual-agent therapy.54–57 Other case series have reported the use of sildenafil in combination with infused therapy to successfully wean to oral therapy alone.58–60 Although the specific infused prostanoid–oral therapy combination used in these studies differed, these case series provide additional support for the safety and feasibility of treatment approaches involving combinations of agents.

  • Hemodynamic Stability After Transitioning Between Endothelin Receptor Antagonists in Patients With Pulmonary Arterial Hypertension

    2013, Canadian Journal of Cardiology
    Citation Excerpt :

    First, it is one of the largest series of PAH patients transitioned between approved therapies in general and between oral therapies in particular.12-14 Previously, most studies have reported transition between different parenteral prostanoid analogues (typically epoprostenol to treprostinil) or between parenteral prostanoid analogues and oral therapies.13,18-29 Another study has examined transitioning between an ERA and the phosphodiesterase inhibitor, sildenafil.30

  • Successful Up-front Combination Therapy in a Patient With Idiopathic Pulmonary Hypertension and Patent Foramen Ovale: An Alternative to Epoprostenol Therapy?

    2009, Journal of Heart and Lung Transplantation
    Citation Excerpt :

    The acute vasodilator effects of sildenafil are at least as strong as those achieved with inhaled nitric oxide at clinically relevant doses.5 Moreover, sildenafil increases and prolongs the effects of inhaled iloprost,6 while the transition from subcutaneous treprostionil to sildenafil has proven to be safe in a series of patients with PAH of varied etiology.7 In a previous report, administration of sildenafil in an iPAH patient with PFO resulted in dramatic improvement in PH and right-sided heart failure and disappearance of the right-to-left shunt throughout the PFO.8

View all citing articles on Scopus

Supported in part by an unrestricted educational grant and a supply of sildenafil from Pfizer Australia Pty, Ltd.

View full text